Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats

The aim of the present study was to investigate the relationship between ph ysical abstinence and changes in dopamine release in the nucleus accumbens and in the medial prefrontal cortex induced by mecamylamine and naloxone in rats chronically exposed to nicotine. The rats were implanted with osmotic minipumps (Alzet) delivering nicotine tartrate at a rate of 9 mg/kg/day (3 .16 mg of free base) and 8 days later with a dialysis probe in the nucleus accumbens or in the medial prefrontal cortex. Steady-state dopamine output from the nucleus accumbens of the rats implanted with nicotine minipumps wa s higher than that of sham implanted rats; no differences were observed in the prefrontal cortex. In nicotine but not in sham implanted rats mecamylam ine (1 mg/kg s.c.) precipitated a physical abstinence syndrome and brought dopamine output back to control values in the nucleus accumbens. In contras t mecamylamine (1 mg/kg s.c.) increased dopamine output in the medial prefr ontal cortex of nicotine but not sham-implanted rats. Naloxone (2 mg/kg) pr ecipitated a physical abstinence syndrome qualitatively similar to that pro duced by mecamylamine but failed to modify extracellular dopamine in the nu cleus accumbens or in the prefrontal cortex of nicotine-implanted and sham- implanted rats. The results indicate that the mesolimbic and mesocortical d opamine system undergo opposite changes during mecamylamine-precipitated ab stinence in rats chronically exposed to nicotine and that physical abstinen ce signs can be dissociated from changes in dopamine transmission. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.